Variant rs3729992 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000257.4(MYH7):c.-8-25G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,610,064 control chromosomes in the GnomAD database, including 4,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 366 hom., cov: 33)

Exomes 𝑓: 0.073 ( 4050 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.792

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-23433765-C-A is Benign according to our data. Variant chr14-23433765-C-A is described in ClinVar as [Benign]. Clinvar id is 1174731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23433765-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4 linkuse as main transcript	c.-8-25G>T		intron_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1 linkuse as main transcript	c.-8-25G>T		intron_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4 linkuse as main transcript	c.-8-25G>T		intron_variant		1	NM_000257.4	ENSP00000347507	P1

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9547

AN:

152210

Hom.:

367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.0748

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.0981

Gnomad FIN

AF:

0.0523

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0755

Gnomad OTH

AF:

0.0717

GnomAD3 exomes

AF:

0.0699

AC:

17341

AN:

248174

Hom.:

716

AF XY:

0.0736

AC XY:

9896

AN XY:

134414

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0563

Gnomad SAS exome

AF:

0.0991

Gnomad FIN exome

AF:

0.0558

Gnomad NFE exome

AF:

0.0766

Gnomad OTH exome

AF:

0.0804

GnomAD4 exome

AF:

0.0727

AC:

105968

AN:

1457736

Hom.:

4050

Cov.:

AF XY:

0.0740

AC XY:

53669

AN XY:

725392

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.0478

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.0379

Gnomad4 SAS exome

AF:

0.0982

Gnomad4 FIN exome

AF:

0.0584

Gnomad4 NFE exome

AF:

0.0741

Gnomad4 OTH exome

AF:

0.0728

GnomAD4 genome

AF:

0.0626

AC:

9541

AN:

152328

Hom.:

366

Cov.:

AF XY:

0.0618

AC XY:

4602

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0282

Gnomad4 AMR

AF:

0.0747

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0574

Gnomad4 SAS

AF:

0.0981

Gnomad4 FIN

AF:

0.0523

Gnomad4 NFE

AF:

0.0755

Gnomad4 OTH

AF:

0.0705

Alfa

AF:

0.0722

Hom.:

438

Bravo

AF:

0.0603

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over